This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Every day we are becoming more aware of the host of human health problems associated with metal toxicity, either from environmental exposure or from errant metal metabolism. These concerns have prompted scientists to look for examples of organisms that are able to thrive in the presence of toxic levels of metals and to explore the broad range of molecular mechanisms that maintain metal homeostasis. Metal-tolerant organisms might be exploited for bioremediation, but not without first understanding the molecular basis for their vitality. This proposal focuses on a few of the many diverse approaches towards controlling metal toxicity in the biosphere. Our first subproject is focused on the sequestering of lead and cadmium by Acanthocephalans parasitic worms. By identifying the molecular mechanisms by which these parasites take up and sequester heavy metals, the potential exists for the development of powerful new biomarkers, of new bioremediation strategies, and of alternative detoxification therapies. A second subproject explores the role and structure of copper chaperones in Methylococcus capsulatus (Bath) and in the thermophile Archaeglobus fulgidus. A third project focuses on the gene products of the Staphylococcus aureus plasmid pI258 that confer cadmium tolerance to this organism.